tbuckley/cabot-search huggingface dataset:
Excess All-Cause Mortality in China After Ending the Zero COVID Policy
Authors: Hong Xiao, Zhicheng Wang, Fang Liu, Joseph M. Unger
Journal: JAMA Network Open (2023)

In China, the implementation of stringent mitigation measures kept COVID-19 incidence and excess mortality low during the first years of the pandemic. However, China's decision to end its dynamic zero COVID policy (a proactive strategy that deploys mass testing and strict quarantine measures to stamp out any outbreak before it can spread) in December 2022 resulted in a surge in COVID-19 incidence and hospitalizations. Despite worldwide attention given to this event, the actual impact of this sudden shift in policy on population mortality has not been empirically estimated.To assess the association of the sudden shift in China's dynamic zero COVID policy with mortality using empirical and syndromic surveillance data.This cohort study analyzed published obituary data from 3 universities in China (2 in Beijing and 1 in Heilongjiang) and search engine data from the Baidu index (BI; weighted frequency of unique searches for a given keyword relative to the total search volume on the Baidu search engine) in each region of China from January 1, 2016, to January 31, 2023. Using an interrupted time-series design, analyses estimated the relative change in mortality among individuals 30 years and older in the universities and the change in BI for mortality-related terms in each region of China from December 2022 to January 2023. Analysis revealed a strong correlation between Baidu searches for mortality-related keywords and actual mortality burden. Using this correlation, the relative increase in mortality in Beijing and Heilongjiang was extrapolated to the rest of China, and region-specific excess mortality was calculated by multiplying the proportional increase in mortality by the number of expected deaths. Data analysis was performed from February 10, 2023, to March 5, 2023.The end to the dynamic zero COVID policy in December 2022 in China.Monthly all-cause mortality by region.An estimated 1.87 million (95% CI, 0.71 million-4.43 million; 1.33 per 1000 population) excess deaths occurred among individuals 30 years and older in China during the first 2 months after the end of the zero COVID policy. Excess deaths predominantly occurred among older individuals and were observed across all provinces in mainland China except Tibet.In this cohort study of the population in China, the sudden lifting of the zero COVID policy was associated with significant increases in all-cause mortality. These findings provide valuable insights for policy makers and public health experts and are important for understanding how the sudden propagation of COVID-19 across a population may be associated with population mortality.
Self-care treatment for lymphoedema of lymphatic filariasis using integrative medicine
Authors: Saravu R Narahari, Madhur G Aggithaya, Terence J Ryan, Kunnathody Muralidharan, Peter J Franks, Christine Moffatt, Peter S Mortimer
Journal: British Journal of Dermatology (2023)

Lymphatic filariasis (LF) is a neglected tropical disease presenting mainly as lymphoedema (elephantiasis). At present, LF is not effectively treated. Integrative medicine (IM) treatment for lymphoedema uses a combination of Indian traditional medicine, Ayurveda, alongside yoga exercises, compression therapy, antibiotics and antifungal treatments, providing a useful combination where resources are limited and different practices are in use.
Midpregnancy Phthalate and Phenol Biomarkers in Relation to Infant Body Composition: The Healthy Start Prospective Cohort
Authors: Danielle R. Stevens, Anne P. Starling, Paige A. Bommarito, Alexander P. Keil, Dorothy Nakiwala, Antonia M. Calafat, John L. Adgate, Dana Dabelea, Kelly K. Ferguson
Journal: Environmental Health Perspectives (2023)

Background: Gestational phthalate and phenol exposure disrupts adipogenesis, contributing to obesity in mice. Whether gestational phthalate or phenol exposure is associated with infant body composition has not been investigated in humans. Objective: We examined associations between biomarkers of phthalate and phenol exposure in midpregnancy and infant size and body composition at birth and at 5 months of age. Methods: Analyses were conducted among 438 infants from the Healthy Start prospective pregnancy cohort. Sixteen phthalate and phenol biomarkers were quantified in spot urine samples collected at 24–28 wk of gestation. Infant outcomes measured at birth and at 5 months of age included size [weight (in grams)] and body composition [fat and lean masses (in grams); percentage fat mass]. Single- (linear) and multipollutant (quantile g-computation) models were used to estimate associations of phthalate and phenol biomarkers with infant outcomes at birth and at 5 months of age. Models were adjusted for sociodemographics, sample collection timing, and lifestyle factors and used to examine for effect modification by infant sex. Results: In single-pollutant models, mono-benzyl phthalate and di-n-butyl phthalate were inversely associated with percentage fat mass [β: −0.49 (95% CI: −0.91, −0.08) and −0.51 (95% CI: −1.02, 0.01), respectively] in male but not female infants at birth. Similar, but less precise, associations were observed at 5 months of age. In multipollutant models, a 1-quartile increase in the phthalate and phenol biomarker mixture was inversely associated with percentage fat mass at birth [−1.06 (95% CI: −2.21, 0.1)] and at 5 months of age [−2.14 (95% CI: −3.88, −0.39)] among males, but associations were null among females [0.48 (95% CI: −0.78, 1.75) and −0.64 (95% CI: −2.68, 1.41), respectively]. Similar associations were observed with infant weight. Conclusion: In this U.S.-based prospective cohort, gestational phthalate and phenol biomarkers were inversely associated with infant weight and fat mass, particularly in males. https://doi.org/10.1289/EHP12500
Peroxisome disruption alters lipid metabolism and potentiates antitumor response with MAPK-targeted therapy in melanoma
Authors: Fan Huang, Feiyang Cai, Michael S. Dahabieh, Kshemaka Gunawardena, Ali Talebi, Jonas Dehairs, Farah El-Turk, Jae Yeon Park, Mengqi Li, Christophe Goncalves, Natascha Gagnon, Jie Su, Judith H. LaPierre, Perrine Gaub, Jean-Sébastien Joyal, John J. Mitchell, Johannes V. Swinnen, Wilson H. Miller, Sonia V. del Rincón
Journal: Journal of Clinical Investigation (2023)

Melanomas reprogram their metabolism to rapidly adapt to therapy-induced stress conditions, allowing them to persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKis) through a concerted metabolic reprogramming mediated by peroxisomes and UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, by repressing PEX3 expression, potentiated the proapoptotic effects of MAPKis via an induction of ceramides, an effect limited by UGCG-mediated ceramide metabolism. Cotargeting PEX3 and UGCG selectively eliminated a subset of metabolically active, drug-tolerant CD36+ melanoma persister cells, thereby sensitizing melanoma to MAPKis and delaying resistance. Increased levels of peroxisomal genes and UGCG were found in patient-derived MAPKi-relapsed melanomas, and simultaneously inhibiting PEX3 and UGCG restored MAPKi sensitivity in multiple models of therapy resistance. Finally, combination therapy consisting of a newly identified inhibitor of the PEX3-PEX19 interaction, a UGCG inhibitor, and MAPKis demonstrated potent antitumor activity in preclinical melanoma models, thus representing a promising approach for melanoma treatment.
Optimizing Longitudinal Tobacco Cessation Treatment in Lung Cancer Screening
Authors: Steven S. Fu, Alexander J. Rothman, David M. Vock, Bruce R. Lindgren, Daniel Almirall, Abbie Begnaud, Anne C. Melzer, Kelsey L. Schertz, Mariah Branson, David Haynes, Patrick Hammett, Anne M. Joseph
Journal: JAMA Network Open (2023)

Importance Nearly half of the 14.8 million US adults eligible for lung cancer screening (LCS) smoke cigarettes. The optimal smoking cessation program components for the LCS setting are unclear. Objective To assess the effect of adding a referral to prescription medication therapy management (MTM) to the tobacco longitudinal care (TLC) program among patients eligible for LCS who smoke and do not respond to early tobacco treatment and to assess the effect of decreasing the intensity of TLC among participants who do respond to early treatment. Design, Setting, and Participants This randomized clinical trial included patients who currently smoked cigarettes daily and were eligible for LCS. Recruitment took place at primary care centers and LCS programs at 3 large health systems in the US and began in October 2016, and 18-month follow-up was completed April 2021. Interventions (1) TLC comprising intensive telephone coaching and combination nicotine replacement therapy for 1 year with at least monthly contact; (2) TLC with MTM, MTM offered pharmacist-referral for prescription medications; and (3) Quarterly TLC, intensity of TLC was decreased to quarterly contact. Intervention assignments were based on early response to tobacco treatment (abstinence) that was assessed either 4 weeks or 8 weeks after treatment initiation. Main outcomes and Measures Self-reported, 6-month prolonged abstinence at 18-month. Results Of 636 participants, 228 (35.9%) were female, 564 (89.4%) were White individuals, and the median (IQR) age was 64.3 (59.6-68.8) years. Four weeks or 8 weeks after treatment initiation, 510 participants (80.2%) continued to smoke (ie, early treatment nonresponders) and 126 participants (19.8%) had quit (ie, early treatment responders). The 18 month follow-up survey response rate was 83.2% (529 of 636). Across TLC groups at 18 months follow-up, the overall 6-month prolonged abstinence rate was 24.4% (129 of 529). Among the 416 early treatment nonresponders, 6-month prolonged abstinence for TLC with MTM vs TLC was 17.8% vs 16.4% (adjusted odds ratio [aOR] 1.13; 95% CI, 0.67-1.89). In TLC with MTM, 98 of 254 participants (39%) completed at least 1 MTM visit. Among 113 early treatment responders, 6-month prolonged abstinence for Quarterly TLC vs TLC was 24 of 55 (43.6%) vs 34 of 58 (58.6%) (aOR, 0.54; 95% CI, 0.25-1.17). Conclusions and Relevance In this randomized clinical trial, adding referral to MTM with TLC for participants who did not respond to early treatment did not improve smoking abstinence. Stepping down to Quarterly TLC among early treatment responders is not recommended. Integrating longitudinal tobacco cessation care with LCS is feasible and associated with clinically meaningful quit rates. Trial Registration ClinicalTrials.gov Identifier: NCT02597491
Circulating mast cell progenitors increase during natural birch pollen exposure in allergic asthma patients
Authors: P. Abigail Alvarado‐Vazquez, Erika Mendez‐Enriquez, Maya Salomonsson, Ida Waern, Christer Janson, Sara Wernersson, Andrei Malinovschi, Jenny Hallgren
Journal: Allergy (2023)

Mast cells (MCs) develop from a rare population of peripheral blood circulating MC progenitors (MCps). Here, we investigated whether the frequency of circulating MCps is altered in asthma patients sensitized to birch pollen during pollen season, compared to out of season.Asthma patients were examined during birch pollen season in late April to early June (May), and out of season in November-January. Spirometry measurements, asthma and allergy-related symptoms, asthma control questionnaire (ACQ), and asthma control test (ACT) scores were assessed at both time points. The MCp frequency was determined by flow cytometry in ficoll-separated blood samples from patients with positive birch pollen-specific IgE, and analyzed in relation to basic and disease parameters.The frequency of MCps per liter of blood was higher in May than in November (p = .004), particularly in women (p = .009). Patients that reported moderate to severe asthma symptoms (<.0001), nose or eye symptoms (p = .02; p = .01), or reduced asthma control (higher ACQ, p = .01) had higher MCp frequency in May than those that did not report this. These associations remained significant after adjusting for sex and BMI. The change in asthma control to a lower ACT score in May correlated with an increase in MCp frequency in May (p = .006, rho = 0.46).The data suggest that the frequency of MCps increases in symptomatic patients with allergic asthma. Our results unravel a link between asthma symptoms and circulating MCps, and bring new insight into the impact of natural allergen exposure on the expansion of MCs.
Hematopoietic-specific heterozygous loss of <i>Dnmt3a</i> exacerbates colitis-associated colon cancer
Authors: Yang Feng, Qingchen Yuan, Rachel C. Newsome, Troy Robinson, Robert L. Bowman, Ashley N. Zuniga, Kendra N. Hall, Cassandra M. Bernsten, Daniil E. Shabashvili, Kathryn I. Krajcik, Chamara Gunaratne, Zachary J. Zaroogian, Kartika Venugopal, Heidi L. Casellas Roman, Ross L. Levine, Walid K. Chatila, Rona Yaeger, Alberto Riva, Christian Jobin, Daniel Kopinke, Dorina Avram, Olga A. Guryanova
Journal: The Journal of Experimental Medicine (2023)

Clonal hematopoiesis (CH) is defined as clonal expansion of mutant hematopoietic stem cells absent diagnosis of a hematologic malignancy. Presence of CH in solid tumor patients, including colon cancer, correlates with shorter survival. We hypothesized that bone marrow–derived cells with heterozygous loss-of-function mutations of DNMT3A, the most common genetic alteration in CH, contribute to the pathogenesis of colon cancer. In a mouse model that combines colitis-associated colon cancer (CAC) with experimental CH driven by Dnmt3a+/Δ, we found higher tumor penetrance and increased tumor burden compared with controls. Histopathological analysis revealed accentuated colonic epithelium injury, dysplasia, and adenocarcinoma formation. Transcriptome profiling of colon tumors identified enrichment of gene signatures associated with carcinogenesis, including angiogenesis. Treatment with the angiogenesis inhibitor axitinib eliminated the colon tumor-promoting effect of experimental CH driven by Dnmt3a haploinsufficiency and rebalanced hematopoiesis. This study provides conceptually novel insights into non-tumor-cell-autonomous effects of hematopoietic alterations on colon carcinogenesis and identifies potential therapeutic strategies.
Artificial Intelligence—From Starting Pilots to Scalable Privilege
Authors: Atul J. Butte
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Nanocages and cell‐membrane display technology as smart biomaterials
Authors: Yulan Wang, Richard J. Miron, Xiaoxin Zhang, Hao Zeng, Yufeng Zhang
Journal: Periodontology 2000 (2023)

Abstract Gold nanocages (AuNCs) have been invented and developed over two decades as biomaterial in clinical medicine with great application potential. AuNCs have a characteristic structure of porous walls with hollow interior and a compact size. This makes it possible for them to transport biomolecules or drugs with the advantages of their photothermal effects that could help further destroy germs or tumors while also regulating the release of drugs inside. Furthermore, their bioactivity and application can be broadened by using cell‐membrane display technology. AuNCs have shown tremendous potential in antibacterial activity, inflammation modulation, and tissue regeneration, which is required in periodontitis and peri‐implantitis treatment. Thus, this article provides an overview of AuNCs synthesis, characteristics, surface modifications, and clinical applications, aiming to serve as a reference for the design and fabrication of AuNCs‐based smart materials for periodontal or peri‐implant application.
Advances in single-cell RNA sequencing and its applications in cancer research
Authors: Dezhi Huang, Naya Ma, Xinlei Li, Yang Gou, Yishuo Duan, Bangdong Liu, Jing Xia, Xianlan Zhao, Xiaoqi Wang, Qiong Li, Jun Rao, Xi Zhang
Journal: Journal of Hematology & Oncology (2023)

Abstract Cancers are a group of heterogeneous diseases characterized by the acquisition of functional capabilities during the transition from a normal to a neoplastic state. Powerful experimental and computational tools can be applied to elucidate the mechanisms of occurrence, progression, metastasis, and drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect the average gene expression in a sample, making it difficult to understand tumor heterogeneity and the tumor microenvironment. The emergence and development of single-cell RNA sequencing (scRNA-seq) technologies have provided opportunities to understand subtle changes in tumor biology by identifying distinct cell subpopulations, dissecting the tumor microenvironment, and characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used in cancer studies to explore tumor heterogeneity and the tumor microenvironment, which has increased the understanding of tumorigenesis and evolution. This review summarizes the basic processes and development of scRNA-seq technologies and their increasing applications in cancer research and clinical practice.
Unveiling the complex relationship between gut microbiota and liver cancer: opportunities for novel therapeutic interventions
Authors: Jayashi Rajapakse, Saroj Khatiwada, Anna Camille Akon, Kin Lam Yu, Sj Shen, Amany Zekry
Journal: Gut Microbes (2023)

Hepatocellular carcinoma (HCC) has been linked to the gut microbiota, with recent studies revealing the potential of gut-generated responses to influence several arms of the immune responses relevant to HCC formation. The pro- or anti-tumor effects of specific bacterial strains or gut microbiota-related metabolites, such as bile acids and short-chain fatty acids, have been highlighted in many human and animal studies. The critical role of the gut microbiota in HCC development has spurred interest in modulating the gut microbiota through dietary interventions, probiotics, and fecal microbiota transplantation as a potential strategy to improve liver cancer outcomes. Encouragingly, preclinical and clinical studies have demonstrated that modulation of the gut microbiota can ameliorate liver function, reduce inflammation, and inhibit liver tumor growth, underscoring the potential of this approach to improve HCC outcomes. As research continues to unravel the complex and dynamic mechanisms underlying the gut-liver axis, the development of safe and effective interventions to target this pathway for liver cancer prevention and treatment appears to be on the horizon, heralding a significant advance in our ongoing efforts to combat this devastating disease.
Bone regeneration in implant dentistry: Which are the factors affecting the clinical outcome?
Authors: Nikolaos Donos, Aliye Akcali, Ninad Padhye, Anton Sculean, Elena Calciolari
Journal: Periodontology 2000 (2023)

Abstract The key factors that are needed for bone regeneration to take place include cells (osteoprogenitor and immune‐inflammatory cells), a scaffold (blood clot) that facilitates the deposition of the bone matrix, signaling molecules, blood supply, and mechanical stability. However, even when these principles are met, the overall amount of regenerated bone, its stability over time and the incidence of complications may significantly vary. This manuscript provides a critical review on the main local and systemic factors that may have an impact on bone regeneration, trying to focus, whenever possible, on bone regeneration simultaneous to implant placement to treat bone dehiscence/fenestration defects or for bone contouring. In the future, it is likely that bone tissue engineering will change our approach to bone regeneration in implant dentistry by replacing the current biomaterials with osteoinductive scaffolds combined with cells and mechanical/soluble factors and by employing immunomodulatory materials that can both modulate the immune response and control other bone regeneration processes such as osteogenesis, osteoclastogenesis, or inflammation. However, there are currently important knowledge gaps on the biology of osseous formation and on the factors that can influence it that require further investigation. It is recommended that future studies should combine traditional clinical and radiographic assessments with non‐invasive imaging and with patient‐reported outcome measures. We also envisage that the integration of multi‐omics approaches will help uncover the mechanisms responsible for the variability in regenerative outcomes observed in clinical practice.